Niacin Flushing as Marker of Cannabis Effects on Arachidonic Acid Pathways in Schizophrenia
Information source: University of Jena
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia; Cannabis Abuse
Phase: N/A
Status: Completed
Sponsored by: University of Jena Official(s) and/or principal investigator(s): Heinrich Sauer, PhD, Study Director, Affiliation: University of Jena
Summary
Increasing evidence suggests modulating effects of cannabinoids on time of onset, severity,
and outcome of schizophrenia. Efforts to discover the underlying pathomechanism have led to
the assumption of gene x environment interactions including premorbid genetical
vulnerability and worsening effects of continuing cannabis use. For a main characteristic of
psychoactive delta-9-tetrahydrocannabinol is its affinity to biological membranes, which are
known to be disturbed in schizophrenia patients and genetic high-risk populations.
Here we assess an hypothesised association between premorbid lipid disturbance and metabolic
effects of external cannabinoids in schizophrenia.
Intensity of niacin (methylnicotinate) skin flushing, indicating disturbed
prostaglandin-mediated processes, is used as peripheral marker of lipid-arachidonic acid
pathways and investigated in cannabis consuming and non-consuming schizophrenia patients and
in healthy controls. Methylnicotinate is applied in three concentrations onto the forearm
skin. Flush response is assessed in three minute intervals over 15 min using optical
reflection spectroscopy.
Clinical Details
Official title: First Detailed Study on Effects of Long Term Regular Cannabis Use on Arachidonic Acid-Prostaglandine Pathways in Schizophrenia
Study design: Observational Model: Defined Population, Time Perspective: Cross-Sectional
Detailed description:
Subjects Niacin skin tests are performed on acutely ill consecutively admitted schizophrenia
patients suffering not more than two psychotic episodes. All meet DSM-IV criteria for
paranoide schizophrenia. Diagnosis is made by two independent experienced psychiatrists and
further supported by structured clinical interview (SCID IV) (Wittchen et al 1997). Majority
of patients is treated mostly with atypical neuroleptic drugs. The patient population is
subdivided in one group having used cannabis on a regular basis (≥ 0,5 g/d, at least 3
month) prior to admission, and another group having never used cannabis apart from unique
trials. Cannabis consuming patients do not use any other drug or alcohol on a regular basis.
Psychiatric symptoms are assessed using Brief Psychiatric Rating Scale (BPRS) (Overall and
Gorham 1962), Scale of Assessment of Positive Symptoms (SAPS) (Andreasen 1984), Scale of
Assessment of Negative Symptoms (SANS) (Andreasen 1983), and Symptom Check List 1990 Revised
(SCL 90-R) (Kaplan et al 1998).
Patients are compared to healthy volunteers recruited by newspaper advertisement including
again one group of cannabis users (duration and dose of cannabis use as in patients) and one
group without any cannabis experience. Controls are interviewed in-depth to rule out a
current psychiatric diagnosis or psychiatric personal or family history. As in patients, SCL
90-R is also applied in controls.
All cannabis-using participants are tested positive for cannabinoids in urine at the time of
niacin testing. Subjects with any current or history of skin disorders (eczema, atopical
dermatitis, psoriasis) or recent treatment with steroids or non-steroidal antiinflammatory
drugs (e. g. acetylsalicylic acid) are excluded from the study before niacin testing. The
study is approved by the Ethics Committee of Friedrich-Schiller-University Jena. All
participants give written informed consent to participate in the study.
Niacin skin test protocol Methylnicotinate (C7H7NO2, 99%, Sigma-ALDRICH Chemie GmbH,
Germany) is applied simultaneously in three dilutions (0. 001 M, 0. 01 M, 0. 1 M) of 50 µl each
to the skin at the inner side of the forearm using chambered plaster for epicutaneous
testing. After 90 sec the plaster is removed. Skin flushing is quantified before and up to
15 minutes after methylnicotinate exposure in 3-min intervals, starting 90 sec after removal
of the methylnicotinate patches. Methylnicotinate solutions are freshly prepared for each
test to prevent any influence of sunlight.
Reflection spectroscopy Optical reflection spectroscopy (ORS) is applied as described in
more detail by Smesny et al 2001. Skin content of oxygenated blood is assessed with a
handheld optical reflection spectrometer (spectral range: 400 nm to 700 nm, area of
measurement: diameter 5 mm), using the oxyhemoglobin (HbO2) absorption double peak at 542 nm
and 577 nm. Each measurement is repeated three times (within 10 sec) and then averaged.
Spectroscopic data are processed automatically creating difference spectra by subtraction of
pre-stimulation reflection intensities (also measured three times) from test intensities.
Two Gaussian curves are fitted to the HbO2-absorption double peak. The area under the
resulting sum curve is taken as measure of current skin flushing (measured in arbitrary
units [a. u.]).
Data analysis We plan to conduct a repeated measure analysis of variance (ANOVA) with TIME
(3, 6, 9, 12, 15 min) and methylnicotinate CONCENTRATION (0. 001 M, 0. 01 M, 0. 1 M) as
within-subject factors and GROUP (patients, controls) and CANNABIS (cannabis user, cannabis
non-user) as between subjects factors. GENDER, and AGE are treated as co-variates. For
post-hoc comparison of single values, Mann-Whitney-U-Tests are calculated.
Psychopathological ratings of the SCL 90-R are compared between groups using an univariate
ANOVA with the same between group factors (GROUP, CANNABIS) and co-variates (AGE, GENDER) as
above. Furthermore, effects of cannabis use on SAPS, SANS, and BPRS are investigated within
the patient group. In order to explore a possible association between age or
psychopathological ratings and skin flushing, Spearman correlation coefficients will be
calculated. Due to the high number of calculated coefficients the significance level will be
set on p < 0. 01.
Eligibility
Minimum age: 18 Years.
Maximum age: 40 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Patients:
- acutely ill
- consecutively admitted
- diagnosis of schizophrenia according to DSM-IV criteria for paranoide schizophrenia.
- not treated or treated with atypical neuroleptic drugs
- cannabis use on a regular basis (≥ 0,5 g/d, at least 3 month) prior to admission or
- never use of cannabis apart from unique trials
- no use of any other drug or alcohol on a regular basis.
Controls:
- healthy volunteers recruited by newspaper advertisement
- cannabis user (duration and dose of cannabis use as in patients)or
- no cannabis experience at all
All cannabis consuming participants:
- positive for cannabinoids in urine test at the time of niacin testing
Exclusion Criteria:
Controls:
- current psychiatric diagnosis or psychiatric personal or family history.
All individuals:
- any current or history of skin disorders (eczema, atopical dermatitis, psoriasis)
- recent treatment with steroids or non-steroidal antiinflammatory drugs (e. g.
acetylsalicylic acid)
Locations and Contacts
University of Jena, Department of Psychiatry, Jena, Thueringen D-07743, Germany
Additional Information
Starting date: February 2004
Last updated: October 11, 2006
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